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The princess was born at Rigshospitalet, the Copenhagen University Hospital, in Copenhagen, at 4:02 pm. She was healthy with an apgar score of 10 (out of 10) after 1 minute. At birth, she weighed 3.35 kg (7.4 lb) and measured 50 cm (19.6 ins). At noon on 22 April, a 21-gun salute was fired from the Sixtus Battery at Holmen Naval Base in Copenhagen and from Kronborg Castle in North Zealand to mark the arrival of a royal child.

The infant princess' birth coincided with the 60th anniversary of the ascension to the Danish throne of her great-grandfather, Frederick IX. She her shares birthday with third cousin-twice removed, Queen Elizabeth II.

Isabella's christening took place on 1 July 2007, at the chapel of Fredensborg Palace. She wore the same christening gown her older brother, Prince Christian, had worn at his christening the year before and that Glücksborg princes and princesses in the main line had worn since the christening of Christian X in 1870. Her name was announced as Isabella Henrietta Ingrid Margrethe. Her godparents are The Duchess of Brabant, Princess Alexia of Greece and Denmark, Nadine Johnston, Christian Buchwald, Peter Heering and Marie Louise Skeel.

She was named:

Isabella is the Italian form of the Latinate name Elisheva, which has a biblical etymology and many variants in different languages. The Crown Princess's middle name is Elizabeth after her maternal grandmother; however, there is no indication that this was a factor in the choice of names. Frederik and Mary told the media on the day of the christening they had decided on it two weeks beforehand, after looking at historical royal Danish names. They chose the birth name of King Christian II's queen-consort Isabella of Austria, the sister of Emperor Charles V. The name ranks 16th in popularity for Danish girls born in 2007.

Henrietta is for the Crown Princess's late mother, Henrietta Donaldson, who died in 1997 from complications following heart surgery.

Ingrid is for the Crown Prince's late maternal grandmother, Ingrid of Sweden, who died in November 2000.

Margrethe is for Princess Isabella's paternal grandmother, the Queen of Denmark.

The princess accompanied her parents to New York on 17–21 September 2007 on a visit to promote Denmark's "Creative Nation" initiative, according to court spokeswoman Lis M. Frederiksen, because Crown Princess Mary was still breastfeeding Princess Isabella.

On 20 December 2007, as he had done the previous year for Prince Christian, Per Stig Møller, Denmark's Minister for Foreign Affairs, formally wrote and signed a hand-written document adding Princess Isabella as an official heir to the Danish throne in the line of succession. The princess's full name, dates of birth and christening, and the names of her godparents were recorded as dictated by the Royal Law of 1799.